X-ray crystallographic techniques are being used to study the structural basis of some biological processes. In the area of chemical carcinogenesis and mutagenesis we are studying the structures of some carinogenic polycyclic aromatic hydrocarbons (PAHs), particularly those with methyl groups in the bay region, in order to find the variability that occurs in this region. We are also determining the structures of activated metabolites of these PAHs in order to determine the factors that control conformation in these compounds (diols and diol epoxides). Our major interest is in the effects of alkylation by the activated PAH on the conformation of DNA. Where does the PAH group lie in the alkylated polynucleotide. Does it intercalate or lie in the groove of DNA. This will be investigated by X-ray studies of small polynucleotides alkylated on one central base. The studies of enzyme mechanisms involves the mode of action of B12 coenzymes and the B12-utilizing enzymes, the factors that control the formation and cleavage of the citrate ion, and the action of certain steriod-utilizing enzymes and the enzymes that activate PAHs. These involve crystal structure determinations of the substrates, inhibitors and also the enzymes. The role of metals in the mode of action of xylose isomerase will also be studied. Preliminary crystallization studies on crystalline enzymes involve yeast aconitase, E. coli citrate synthase, ATP citrate lyase, methyl-malonylCoA mutase, ethanolamine ammonia lyase and ribonucleotide reductase.